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Francisco, M.

Publications and source records attributed to Francisco, M..

2 recordsLinked to original sources

Pregnancy and weaning regulate human maternal liver size and function

BACKGROUNDDuring pregnancy, the rodent liver undergoes hepatocyte proliferation and increases in size, followed by weaning-induced involution via hepatocyte cell death and stromal remodeling, creating a pro-metastatic niche. These data suggest a mechanism for increased liver metastasis in postpartum breast cancer patients. OBJECTIVESInvestigate if the human liver changes in size and function during pregnancy and weaning. METHODSAbdominal imaging was obtained in healthy women at early and late pregnancy, and post-wean. During pregnancy time points, endogenous glucose production was measured and fasting blood taken to measure bile acids. RESULTSIndependent of weight gain, most womens livers increased in size with pregnancy, returning to baseline post-wean. Putative roles for bile acids in liver growth were observed in pregnant women and rodents. CONCLUSIONSThe human liver is regulated by reproductive state with growth during pregnancy and volume loss post-wean. These findings may have broad implications for sex-specific liver diseases and cancer.

physiology

Fine-mapping identifies NAD-ME1 as a candidate underlying a major locus controlling temporal variation in primary and specialized metabolism in Arabidopsis

Plant metabolism is modulated by a complex interplay between internal signals and external cues. A major goal of all quantitative metabolomic studies is to clone the underlying genes to understand the mechanistic basis of this variation. Using fine-scale genetic mapping, in this work we report the identification and initial characterization of NAD-DEPENDENT MALIC ENZYME 1 (NAD-ME1) as the candidate gene underlying the pleiotropic network Met.II.15 QTL controlling variation in plant metabolism and circadian clock outputs in the Bay x Sha Arabidopsis population. Transcript abundance and promoter analysis in NAD-ME1Bay-0 and NAD-ME1Sha alleles confirmed allele-specific expression that appears to be due a polymorphism disrupting a putative circadian cis-element binding site. Analysis of T-DNA insertion lines and heterogeneous inbred families (HIFs) showed that transcript variation of the NAD-ME1 gene led to temporal shifts of tricarboxylic acid cycle (TCA) intermediates, glucosinolate (GSL) accumulation and altered regulation of several GSL biosynthesis pathway genes. Untargeted metabolomics analyses reveal complex regulatory networks of NAD-ME1 dependent upon the day-time. The mutant lead to shifts in plant primary metabolites, cell-wall components, isoprenoids, fatty acids and plant immunity phytochemicals, among others. Our findings suggest that NAD-ME1 may act as a key component to coordinate plant primary and secondary metabolism in a time-dependent manner.

plant biology